Conference Proceedings
Inhibition of RNA polymerase I transcription activates targeted DNA damage response and enhances the efficacy of PARP inhibitors in high-grade serous ovarian cancer.
Elaine Sanij, Katherine Hannan, Jiachen Xuan, Shunfei Yan, Jessica A Ahern, Anna S Trigos, Natalie Brajanovski, Jinbae Son, Keefe T Chan, Olga Kondrashova, Elizabeth Lieschke, Matthew J Wakefield, Sarah Ellis, Carleen Cullinane, Gretchen Poortinga, Kum Kum Khanna, Linda Mileshkin, Grant A McArthur, John Soong, Els M Berns Show all
CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2020
Abstract
Abstract Introduction: PARP inhibitors (PARPi) have revolutionized disease management of patients with homologous recombination (HR) DNA repair-deficient high-grade serous ovarian cancer (HGSOC). However, acquired resistance to PARPi is a major challenge in the clinic. The specific inhibitor of RNA polymerase I (Pol I) transcription of ribosomal RNA genes (rDNA) has demonstrated single-agent antitumor activity in p53 wild-type and p53-mutant hematologic malignancies (first-in-human trial, dose escalation study of CX-5461 at Peter MacCallum Cancer Centre) (Khot et al., Cancer Discov 2019). CX-5461 has also been reported to exhibit synthetic lethality with BRCA1/2 deficiency thr..
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